We herein propose an expeditious synthesis of pentalenolactone, a cytotoxic and structurally unusual acidic lipophilic antibiotic isolated from the fermentation broth of Streptomyces UC 5319. The antibiotic contains five chiral centers and five sites of functionality (carbonyl groups, epoxide, and double bonds) distributed over fifteen carbon atoms which are arranged in a novel pentalene skeleton bearing a fused six membered alpha epoxy lactome moiety. Pentalenolactone thus represents a significant and difficult synthetic challenge both with respect to controlled formation of carbon bonds as well as to the selective manipulation of a variety of functional groups. Although pentalenolactone is a potentially exciting chemotherapeutic agent, it is not available in large amounts and a promising approach to obtain quantities of this material appears to be by total synthesis. We herein propose and expeditious synthesis of pentalenolactone, the salient aspects of which include a Michael addition reaction which introduces thirteen of the fifteen carbon atoms present in pentalenolactone and three of the five chiral centers found in the antibiotic. In addition, a new and potentially general method for the elaboration of alpha epoxy lactones is described. We have entered into a collaborative effort with the Department of Oncology at the University of Rochester to test synthetic pentalenolactone as well as intermediates leading to it. We also intend to submit the same compounds for testing to the Cancer Chemotherapy National Service Center.